1. Field
One embodiment of the present invention relates to a dialysate for preparing a dialysis fluid in which the concentrations of trace metal ions such as potassium ions, calcium ions, and magnesium ions can be maintained at constant levels and the bicarbonate concentration can be suitably changed according to the disease state of a patient. Moreover, one embodiment of the present invention relates to a method and an apparatus for preparing such a dialysis fluid. One embodiment of the present invention relates to a dialysis system that uses such a dialysis fluid and an apparatus.
2. Description of the Related Art
Hemodialysis intended for patients with renal failure is widely performed to remove wastes such as electrolytes and uremic toxins present in patient's blood via a dialyzer based mainly on the principle of diffusion or the like, generally using a dialysis fluid obtained by dissolving/diluting a fluid A (agent A) that contains electrolyte components and a fluid B (agent B) that contains sodium bicarbonate with purified water called RO water that has passed through a reverse osmosis membrane or the like.
The fluid A is provided as a concentrate or powder and often dissolved in RO water when used, and the fluid B also is provided as a concentrate or powder and often dissolved in RO water when used.
The component concentrations of an ordinary bicarbonate dialysis fluid are presented below. Bicarbonate dialysis fluids are roughly classified into acetate ion-containing dialysis fluids and dialysis fluids that do not contain acetate ions, i.e., acetate-free. Practically, bicarbonate dialysis fluids often do not contain citrate ions when containing acetate ions, and do not contain acetate ions when containing citrate ions.
Sodium ions: 120 to 150 mEq/l
Potassium ions: 0.5 to 3.0 mEq/l
Calcium ions: 1.5 to 4.5 mEq/l
Magnesium ions: 0 to 2.0 mEq/l
Chloride ions: 90 to 135 mEq/l
Bicarbonate ions: 20 to 40 mEq/l
Acetate ions: 0 to 12 mEq/l
Citrate ions: 0 to 18 mEq/l
Lactate ions: 0 to 10 mEq/l
Malate ions: 0 to 10 mEq/l
Gluconate ions: 0 to 10 mEq/l
Succinate ions: 0 to 10 mEq/l
Glucose: 0 to 2.5 g/l
Although it is seldom used in Japan now, a formulation called an acetate dialysate was also used in the past, and the widely used acetate dialysate contained neither bicarbonate ions nor citrate ions but 30 to 42.5 mEq/l of acetate ions, and the compositions of other components were the same as those in the aforementioned bicarbonate dialysis fluid (see JP H4-75017B, hereafter referred to as “Patent Literature 1”). Meanwhile, in peritoneal dialysis, the dialysis fluid does not contain potassium ions, and lactic acid, sodium lactate, and the like are used as a pH adjuster and an alkaline agent.
Dialysis fluids have the above-described history, and hemodialysis fluids for use particularly in patients with renal failure in Japan are often produced as follows. A powdery agent A generally containing electrolyte components is dissolved in water to give a concentrated fluid A, a powdery agent B composed of sodium bicarbonate is dissolved in water to give a concentrated fluid B, and the concentrated fluids A and B are mixed/diluted in a ratio of fluid A:fluid B:RO water=1:1.26:32.74 using a mixing/diluting apparatus called central dialysis fluid delivery system. The mixture is then supplied to a bedside console through a tube to carry out hemodialysis via a dialyzer.
While a method for dissolving concentrated fluids A and B and a method that uses central dialysis fluid delivery system have been widely used, in some cases concentrated fluids A and B customized for a patient are set in an individual dialysis apparatus at the bedside to use a dialysis fluid having a different formula for every patient. Although individual dialysis apparatuses are used less often than multipatient dialysis apparatus in Japan, it is very common to use an individual dialysis apparatus overseas, and the mixing ratio of fluid A:fluid B:RO water is sometimes slightly different.
For example, in the case where one unit of central dialysis fluid delivery system is used, a group of patients, e.g., about 30 through 50 patients, are dialyzed with a dialysis fluid having the same composition. The advantage of this method is that producing large amounts of a dialysis fluid having the same composition lessens the labor of medical staff. However, the biocompatibility of the dialysis fluid to individual patients is ignored, and a dialysis fluid that has a composition thought to be mostly compatible to all patients is used.
On the other hand, use of an individual dialysis system has an advantage of allowing selection of a dialysis fluid that has a different composition suitable for every patient, but it is necessary to prepare concentrated fluids A and B for every patient, i.e., for every individual dialysis apparatus, and to control the concentration of the dialysis fluid in the individual dialysis apparatus, and thus the burden of medical staff is significant.
Regarding the current situation of dialysis fluids, a brief discussion of conventional art will now be presented below, including cases in Europe and America.
JP H6-245995A (hereafter referred to as “Patent Literature 2”) discloses a method for preparing a dialysis fluid that uses a first or basic concentrate containing sodium chloride and sodium hydrogencarbonate and having a molar ratio of hydrogencarbonate/sodium of 0.3 or less, and a second or individual concentrate containing compositions individually selected according to the physiological requirements to supply the remaining amounts of solutes necessary in the dialysis fluid. The basic concentrate contains 80 to 95% of the total sodium chloride of the final dialysis fluid and serves as a dialysis fluid base, and the individual concentrate containing the remaining 5 to 20% of sodium chloride, potassium, calcium, magnesium, a pH adjuster, and the like is added to the basic concentrate to give the final dialysis fluid. The advantage of this dialysis fluid preparation method is as follows. A basic dialysis fluid is prepared in a central supply unit from the first or basic concentrate, and while causing the basic dialysis fluid to loop-circulate at the bedside of a patient, the second or individual concentrate is supplied before the dialysis fluid reaches a dialyzer, thereby making it possible to select the individual concentrate so as to attain a dialysis fluid composition that is optimum for every patient. Therefore, the method of Patent Literature 2 makes it possible to select potassium, calcium, magnesium, glucose, and the like according to the patient while maintaining the bicarbonate ion concentration in the dialysis fluid at a constant level.
JP Pat. No. 3586767 (hereafter referred to as “Patent Literature 3”) discloses a method for preparing a dialysis fluid that uses a dialysis agent composed of an agent A containing sodium chloride, an agent B composed of sodium bicarbonate, and an agent C containing a calcium salt and a magnesium salt, and that includes continuously dissolving the sodium chloride-containing agent A to a constant concentration in a fluid C in which the agent C is dissolved to a specific concentration and mixing this solution with an agent B solution. The dialysis fluid preparation method described in Patent Literature 3 is mainly intended for individual dialysis apparatus, but is silent as to control of the concentrations of components in the dialysis fluid except for setting the components at predetermined constant concentrations.
Moreover, JP Pat. No. 4235555 (hereafter referred to as “Patent Literature 4”) discloses a method for priming an extracorporeal circuit using a dialysis apparatus that includes a dialysis fluid control system having a supply source of water and separate supply sources of a bicarbonate concentrate and a sodium chloride concentrate, wherein acid and other electrolyte solutions are added in-line to a sodium chloride solution to give a dialysis fluid A, a fluid B in which a bicarbonate concentrate is dissolved is added in-line to the dialysis fluid A, and the mixture is supplied as a dialyzing fluid to a dialyzer by exchange with a priming fluid. However, Patent Literature 4 also does not describe control of the concentrations of components in the dialysis fluid except for setting the components at predetermined constant concentrations.
JP 2005-198943A (hereafter referred to as “Patent Literature 5”) discloses a correction liquid containing potassium chloride, calcium chloride, magnesium chloride, glucose, and the like for a bicarbonate dialysis fluid created by mixing/dilution together with sodium chloride and sodium bicarbonate. Patent Literature 5 does not appear to describe more than obtaining a dialysis fluid having a predetermined constant composition.
As described above, irrespective of multipatient dialysis systems and individual dialysis systems, a dialysis fluid having a constant composition is commonly used, but attempts have been made to select concentrations of calcium, magnesium, potassium, glucose, and the like according to the disease state of an individual.
Meanwhile, as a dialysis fluid to suitably ameliorate metabolic acidosis tailored to individual dialysis patients, a Bifil dialysate has been commercially available. This is composed of a Bifil dialysate, which does not contain an alkaline agent, and a sodium hydrogencarbonate (sodium bicarbonate) replenisher fluid exclusively used for the Bifil dialysate. Dialysis is carried out with the Bifil dialysis fluid, and at the same time the sodium hydrogencarbonate replenisher fluid is continuously introduced into the post-dialyzer blood circuit to ameliorate metabolic acidosis. Use of Bifil is a highly suitable method for ameliorating metabolic acidosis, but because excessively administered sodium hydrogencarbonate easily results in alkalosis, a strict acid-base equilibrium management may be required in one embodiment. In addition to a dialysis operation, an operation to directly inject a replenisher fluid or the like into the blood can easily result in a medical accident, and in fact, a strict warning about medical accidents resulting from use of the Bifil dialysate and sodium hydrogencarbonate replenisher fluid alone is given.